JP2016522401A - Improved ion mobility spectrometer - Google Patents

Abstract

An ion analysis method by ion mobility separation is disclosed. The method includes controlling the amount of charge in the ion trap (3) and then pulsing the ions from the ion trap (3) into the ion mobility separator (5). This makes it possible to control the charge injected into the ion mobility separator (5), so that the space charge interaction between ions distorts the ion mobility peak detected by the detector (7). To prevent it. [Selection] Figure 1

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a priority from UK Patent Application No. 1307404.2 filed on April 24, 2013 and European Patent Application No. 13165210.9 filed on April 24, 2013. And insist on profit. The entire contents of these applications are incorporated herein by reference.

In its simplest form, an ion mobility separator (IMS) comprises an ion pulse source and a drift tube containing a buffer gas or floating gas. An electric field or propagating DC wave is applied along the drift tube to push ions from the ion inlet to the ion outlet of the drift tube. As ions pass through the drift tube, the ions are separated according to their mobility through the buffer gas or floating gas. The velocity (v) of ions with ion mobility (K) in the drift tube with applied electric field (E) is
v = KE
Is calculated by

  Such devices are assembled using an ion guide device in which ions are confined by electrodes. An AC voltage that oscillates at an RF frequency is applied to the electrodes to generate a pseudopotential force that can confine the ions and pass the ions through the ion guidance device for efficient ion propagation.

  The ions are typically separated into an IMS mobility drift tube for analysis, enough to allow ions from one pulse to pass through the packet drift tube before the ions in the next pulse enter the packet drift tube. Be pulsed at regular intervals. In order to maximize the duty cycle of such a device, ions from the ion source are received and trapped upstream of the ion trapping region of the IMS drift tube during the duration between the time when the ions are pulsed into the drift tube. It is known to do. Only a few ions are lost because the ions accumulate in the upstream ion trap during the time that the pre-accumulated ion packet is propagating through the IMS drift tube. The separation time of the first ion pulse in the IMS device is synchronized with the capture and ejection time of the next ion pulse into the IMS drift tube. Thereby, an ion propagation efficiency of almost 100% can be obtained.

  However, improved ion mobility separation methods and improved ion mobility spectrometers that provide improved IMS peak width and more reproducible drift time through the IMS drift tube are desirable.

From the first aspect, the present invention provides an ion analysis method by ion mobility separation or mass separation, the method comprising:
Providing an ion mobility separator separation region (IMS) and an ion trap for discharging ion packets into the IMS;
For each ion packet emitted from the ion trap into the IMS, selecting a predetermined maximum charge desired to be released into the IMS;
Emitting a first ion packet from the ion trap;
Detecting the charge of ions in the first ion packet using a detector;
Determining the difference between the charge detected by the detector and the predetermined maximum charge;
Discharging a second subsequent ion packet from the ion trap into the IMS, wherein the formation of the second ion packet is such that the charge of the ions in the second ion packet is substantially equal to the predetermined maximum charge. Discharging, controlled based on the difference between the charge detected in the first ion packet and the maximum charge to be the same or less than,
including.

  The inventor found that the reproducibility of the ion mobility spectrometer resolution and IMS drift time by avoiding repulsion of ions as they enter the IMS device and while they subsequently pass through the IMS separation region. We recognize that we can raise. The present invention limits the charge from entering the isolation region (ie, the RF closure drift tube) and avoids degradation of IMS performance due to ion repulsion. Specifically, the amount of charge entering the separation region is limited by controlling the amount of charge released from the upstream ion trap into the separation region.

  It is also recognized that when a relatively large number of ions with similar ion mobility pass through the separation region, they repel each other as they move along the separation region, resulting in IMS peak broadening. ing. Preferred embodiments of the present invention overcome such problems.

  In order to avoid the effects of space charge inside it, it is known to limit the charge density within the ion trap and mass analyzer that stores the ions. For example, International Application No. 2004/068523 describes a method for limiting the amount of charge transferred from an ion trap into an ion storage mass analyzer downstream in order to avoid the effects of space charge in the ion storage mass analyzer. Is disclosed. However, the effects of space charge that are widespread within ion traps and ion storage mass analyzers are not considered to be associated with IMS devices for several reasons. For example, ion traps and ion conserving mass analyzers essentially push out ions together in a relatively small volume, where space charge effects are widespread, whereas IMS devices work to separate ions and thus space charge. It is not clear that the consideration of the effect of this applies to IMS devices.

  Moreover, there are no signs and mechanisms of space charge effects in the ion storage device in the IMS device. The effect of space charge in ion storage devices using mass selective ejection methods results in mass shifts that result in loss of mass measurement accuracy and mass resolution. This is due to ions undergoing additional potential due to the ionic environment distorting the confined electric field. This distortion results in a long-term frequency change for each ion, and hence a change in the apparent mass-to-field ratio of the ion. This does not occur in IMS devices that do not confine ions in a small space during analysis and do not depend on the resonance frequency for analysis.

  In addition, most historical data obtained from IMS drift tubes is associated with drift tubes that are not radially confined. The effect of any space charge in such a device will cause the ions to spread radially and have no significant effect on the drift time measured by the device. Therefore, the effect of such space charge will not be recognized.

  Furthermore, the effect of space charge in the ion storage device is caused by the total number of ions present in the trapping region. This is because ions with similar mobility remain in a narrow spatial distribution as they pass through the IMS separation region in an IMS device, so that many ions are localized in regions with similar ion mobility. This is very different from the perception that the effect of space charge will occur. In some situations, the population of ions within a particular mobility region must be controlled independently of the total number of ions ejected into the IMS device.

  For at least the above reasons, the method for reducing the effect of space charge in the ion storage device has not been applied to IMS devices. Thus, it has not previously been recognized that an IMS device would benefit from controlling the amount of charge that enters the device in the manner claimed in the present invention.

  According to the present invention, ion packets are preferably pulsed repeatedly into the IMS device.

  Ions are preferably allowed to enter the ion trap during the ion accumulation period and will be trapped in the ion trap, the first ion packet being accumulated in the ion trap over the first accumulation period, Two ion packets are accumulated in the ion trap over a second accumulation period. The duration of the second accumulation period may be selected or changed for the first accumulation period based on the difference between the charge of the ions detected in the first ion packet and the predetermined maximum charge.

  The duration of the second accumulation period may be reduced relative to the first accumulation period if the charge detected in the first ion packet exceeds a predetermined maximum charge. This allows fewer ions to enter the ion trap during the second accumulation period, thereby reducing the charge of the ions in the second packet. Alternatively, the duration of the second accumulation period may be increased relative to the first accumulation period if the charge detected in the first ion packet is below a predetermined maximum charge. This allows more ions to enter the ion trap during the second accumulation period, thereby increasing the charge of the ions in the second packet.

  Ions are induced at the ion loading rate within the ion trap and are preferably trapped within the ion trap during the ion accumulation period. The first ion packet may be stored in the ion trap at a first ion filling rate, and the second ion packet may be stored in the ion trap at a second ion filling rate. The second fill rate may be selected or changed relative to the first fill rate based on the difference between the charge of the ions detected in the first ion packet and a predetermined maximum charge.

  The second fill rate may be reduced relative to the first fill rate if the charge detected in the first ion packet exceeds a predetermined maximum charge. This allows fewer ions to enter the ion trap during the accumulation period of the second ion packet, thereby reducing the charge of the ions in the second packet. Alternatively, the second fill rate may be increased relative to the first fill rate if the charge detected in the first ion packet is below a predetermined maximum charge. This allows more ions to enter the ion trap during the accumulation period of the second ion packet, thereby increasing the charge of the ions in the second packet.

  Each accumulation period may have the same constant duration.

  Different filling rates can be obtained by attenuating the ions moving towards the ion trap by different amounts.

  Only a portion of the ions in the ion trap can be ejected during the discharge of each ion packet from the ion trap. The size of the portion that is ejected into the second ion packet is within the first ion packet based on the difference between the charge of the ions detected within the first ion packet and a predetermined maximum charge. It can be selected or changed for some size discharged.

  The first ion packet enters the detector after passing through the IMS. The ions are preferably driven by an electric field to pass through the IMS, the ions in the first ion packet are driven with a strong force to pass through the IMS, and the ions in the second ion packet are weak to pass through the IMS. It is driven by. This allows the first ion packet to be swept relatively quickly through the IMS, which is primarily for charge detection and the ions are good in the IMS Can be tolerated because they do not need to be separated. The second ion packet passes through the IMS at a low speed, and the ions in this packet are well separated, so that their ion mobility can be well elucidated.

  A mass analyzer may be provided downstream of the IMS and upstream of the detector for mass analysis of ions passing through the IMS. The mass analyzer may be operated in a first mode such that the first ion packet is not substantially attenuated by the mass analyzer. Or the first ion packet bypasses the mass analyzer and then passes through the detector. The mass analyzer may be operated in a second mode such that the second ion packet is attenuated by the mass analyzer during mass analysis therein. Or the second ion packet does not bypass the mass analyzer. This makes it possible to determine the unattenuated charge of ions in the first ion packet even in the presence of a mass analyzer.

  Alternatively, the mass analyzer and the detector may be provided downstream of the IMS. The first ion packet may be directed to the detector without passing through the mass analyzer. A second ion packet may be directed to the mass analyzer.

  Alternatively, a detector may be provided upstream of the IMS and the first ion packet may be emitted from the ion trap to the detector. Thereby, since the first ion packet does not need to pass through the IMS, the charge can be detected relatively quickly.

  The method uses a detector to detect the charge of the ions in the second ion packet and determines the difference between the charge of the ions detected in the second ion packet and a predetermined maximum charge. And discharging a third subsequent ion packet from the ion trap to the IMS, wherein the formation of the third ion packet is such that the charge of the ions in the third ion packet is a predetermined maximum charge. Control is based on the difference between the charge detected in the second ion packet and a predetermined maximum charge so that it is substantially the same or less.

  The predetermined maximum charge may be the total charge that is desired to be pulsed into all of the ions in the ion packet into the IMS. In this case, the total charge of all ions in the first ion packet is detected by the detector.

  Alternatively, the predetermined maximum charge may be the maximum charge amount of ions within a predetermined drift time range passing through the IMS that is desired to be pulsed into the IMS in an ion packet. In this case, the first ion packet is detected by a detector after the ions have passed through the IMS, and the detector has a charge amount of ions in the first ion packet having a drift time within the predetermined drift time range. And the detected charge is compared to a predetermined maximum charge, and using the comparison, ions in a second ion packet having a drift time within a predetermined drift time range are substantially equal to the predetermined maximum charge. The formation of the second ion packet is controlled so as to have a total charge that is identical or less than the total.

  Alternatively, the predetermined maximum charge may be the maximum charge amount of ions within a predetermined drift time range that passes through the IMS that is desired to be pulsed into the IMS in an ion packet, and the predetermined drift Ions having a time range are assumed to have a predetermined mass to charge ratio range, the first ion packet is mass analyzed, and the total charge of ions in this packet having the predetermined mass to charge ratio range is The detected charge is compared with a predetermined maximum charge, and using the comparison, ions in a second ion packet having a drift time within a predetermined drift time range are substantially equal to the predetermined maximum charge. The formation of the second ion packet is controlled so as to have a total charge that is equal to or less than.

  The ion trap is preferably not continuously filled for the duration between pulses into the IMS.

From the second aspect, the present invention provides an ion analysis method by ion mobility separation or mass separation,
Providing an ion mobility separator separation region (IMS) and an ion trap for discharging ion packets into the IMS;
For each ion packet emitted from the ion trap, selecting a predetermined maximum charge desired to be released into the IMS;
Directing ions from the ion source to the detector and detecting the rate at which charge is received at the detector due to ions from the ion source being detected;
Directing ions from the ion source into the ion trap and trapping ions only during the ion accumulation period;
Select the duration of the ion accumulation period, or the ion trap during the accumulation period so that the charge of the ions trapped in the ion trap is substantially equal to or less than the predetermined maximum charge Controlling the attenuation of ions moving towards
Discharging ions from the ion trap into the IMS;
including.

  The ion source may generate a continuous ion beam that is redirected between the detector and the ion trap.

  A detector is preferably provided upstream of the IMS.

  The predetermined maximum charge is preferably the total charge that is desired to be pulsed into all of the ions in the ion packet and enter the IMS.

  The ion trap is preferably not continuously filled for the duration between pulses into the IMS.

  The method operates in a first mode of operation in which a first electric field condition is applied in the IMS such that ions passing through the IMS separate according to their ion mobility, and ions passing through the IMS Operating in a second mode of operation in which a second electric field condition is applied in the IMS to separate according to the mass-to-charge ratio.

  The present invention can be used to analyze ions by separating ions according to the ion mobility and / or mass to charge ratio of the ions within the IMS separation region. When the first electric field condition is applied across the IMS separation region, ions passing through the buffer gas in the separation region will separate according to their ion mobility. In contrast, if a second field condition is applied across the IMS separation region, ions passing through the buffer gas in the separation region will separate according to their mass-to-charge ratio. The analyzer can be operated in either mode, or can be switched between two modes to perform one mode and then perform the other mode.

  For example, the electric field can be continuously tuned along the separation region to drive ions through a buffer gas in the separation region and cause the ions to separate according to their ion mobility. In this mode, ions move through the separation region at a near steady state speed that depends on their ion mobility in the buffer gas.

  Alternatively, the electric field is applied along the separation region by applying a pulse voltage to the separation region such that ions passing through the separation region are separated according to their ion mobility, as the ions are driven through the separation region. Can be arranged intermittently. In this mode, the electric field that drives the ions through the separation region starts and stops the pulses, so that the ions reach their steady state velocity as they pass through the buffer gas in the separation region. Be disturbed. Therefore, the velocity of ions passing through the separation region decays before the next pulse is applied. This causes the ions to separate according to their mass-to-charge ratio as they pass through the separation region.

  It is contemplated that potential barriers or wells are transported along the isolation region to drive ions through the buffer gas. In the first mode, a relatively slow migration potential barrier or well is used to drive ions through the separation region, so that as the ions pass through the separation region, the ions follow their ion mobility. Can be separated. In the second mode, a relatively fast moving potential barrier or well is used to drive ions through the separation region, so that as the ions pass through the separation region, the ions have their mass-to-charge ratio. Can be separated according to

  The separation region can be operated to achieve ion mobility separation or mass to charge ratio separation according to the techniques disclosed in US Publication No. 2010/0032561.

  The present invention also provides an ion mobility spectrometer or mass spectrometer that is arranged and configured to perform any one of the above methods and that has control means.

Accordingly, the present invention provides an ion mobility spectrometer or mass spectrometer,
An ion mobility separator separation region (IMS), an ion trap and detector for emitting ion packets into the IMS, and
Discharging a first ion packet from the ion trap;
Detecting the charge of the ions in the first ion packet using a detector;
Determining a difference between the charge detected by the detector and a predetermined maximum charge desired to be emitted in the IMS for each ion packet emitted from the ion trap into the IMS; and Between the charge detected in the first ion packet and the predetermined maximum charge so that the charge of the ions in the ion packet is substantially equal to or less than the predetermined maximum charge. Control means arranged and adapted to eject a second subsequent ion packet from the ion trap into the IMS such that formation of the second ion packet is controlled based on the difference.

The present invention also provides an ion mobility spectrometer or mass spectrometer,
An ion source, an ion mobility separator separation region (IMS), an ion trap and a detector for emitting ion packets into the IMS, and
Direct ions from the ion source to the detector, detect the rate at which charge is received at the detector due to ions from the ion source being detected,
Ions from the ion source are guided into the ion trap and captured only during the ion accumulation period
Select the duration of the ion accumulation period, or the charge of ions trapped in the ion trap is substantially the same as the predetermined maximum charge desired to be released into the IMS for each ion packet emitted from the ion trap Control means arranged and adapted to control the attenuation of ions propagating towards the ion trap during the accumulation period and to release ions from the ion trap into the IMS such that they are less than or equal to Is provided.

These mass spectrometers further
(A) (i) Electrospray ionization (“ESI”) ion source, (ii) Atmospheric pressure photoionization (“APPI”) ion source, (iii) Atmospheric pressure chemical ionization (“APCI”) ion source, (iv) Substrate-induced laser desorption ionization (“MALDI”) ion source, (v) laser desorption ionization (“LDI”) ion source, (vi) atmospheric pressure ionization (“API”) ion source, (vii) desorption ionization on silicon (“ DIOS ") ion source, (viii) electron impact (" EI ") ion source, (ix) chemical ionization (" CI ") ion source, (x) field ionization (" FI ") ion source, (xi) field desorption (“FD”) ion source, (xii) inductively coupled plasma (“ICP”) ion source, (xiii) fast atom bombing (“FAB”) ion source, (xiv) liquid second ion Quantity spectrometer (“LSIMS”) ion source, (xv) desorption electrospray ionization (“DESI”) ion source, (xvi) nickel-63 radioactive ion source, (xvii) atmospheric pressure substrate induced laser desorption ionization ion source, ( xviii) thermal spray ion source, (xix) atmospheric extraction glow discharge ionization (“ASGDI”) ion source, (xx) glow discharge (“GD”) ion source, (xxi) impact ion source, (xxii) real-time direct analysis ("DART") ion source, (xxiii) laser atomization ionization ("LSI") ion source, (xxiv) sonic atomization ionization ("SSI") ion source, (xxv) substrate-induced inhalation ionization ("MAII") ion source And (xxvi) an ion source selected from the group consisting of a solvent-induced inhaled ionization (SAII) ion source, and / or (b) One or more continuous or pulsed ion sources, and / or (c) one or more ion guides, and / or (d) one or more ion mobility separators and / or one or more field asymmetric ion mobilities. A spectrometer device, and / or (e) one or more ion traps or one or more ion capture regions, and / or (f) (i) a collision-induced dissociation (“CID”) fission device, (ii) surface triggering Dissociation (“SID”) splitting device, (iii) electron transfer dissociation (“ETD”) splitting device, (iv) electron capture dissociation (“ECD”) splitting device, (v) electron impact or impact dissociation splitting device, (vi ) Photo-induced dissociation (“PID”) splitting device, (vii) laser-induced dissociation splitting device, (viii) infrared radiation-induced dissociation device, (ix) ultraviolet radiation-induced dissociation device, (x) nozzle-skimmer interface Fission device, (xi) intra-source fission device, (xii) intra-source collision induced dissociation fission device, (xiii) thermal or temperature source fission device, (xiv) electric field induced fission device, (xv) magnetic field induced fission device, (xvi) ) An enzymatic digestion or enzyme degradation splitting device, (xvii) an interionic reaction splitting device, (xviii) an ionic molecular reaction splitting device, (xix) an ionic atom reactive splitting device, (xx) an ion metastable ion reactive splitting device, (xxi) An ion metastable molecular reaction splitting device, (xxii) an ion metastable atomic reaction splitting device, (xxiii) an ion-to-ion reaction device for forming an adduct or generating an ion, (xxiv) generating an adduct Or ion molecule reactor for ion reaction to generate ions, (xxv) to generate adducts or to generate ions Ion-atom reactor for on-reaction, (xxvi) Ion-metastable ion reactor for ion reaction to produce adducts or ions, (xxvii) to produce adducts or produce ions Ion-quasi-molecular reactor for ion reaction, (xxviii) Ion-metastable atom reactor for ion reaction to generate adducts or ions, (xxix) Electron ionization dissociation (EID) splitting device One or more collision, splitting or reaction cell selected from: and / or (g) (i) a quadrupole mass analyzer, (ii) a 2D or linear quadrupole mass analyzer, (iii) a pole or 3D quadrupole mass analyzer , (Iv) Penning trap mass analyzer, (v) ion trap mass analyzer, (vi) magnetic compartment mass analyzer, (vii) ion sensor Crotron resonance (“ICR”) mass analyzer, (viii) Fourier transform ion cyclotron resonance (“FTICR”) mass analyzer, (ix) electrostatic or orbital trap mass analyzer, (x) Fourier transform electrostatic or orbital trap Selected from the group consisting of a mass analyzer, (xi) a Fourier transform mass analyzer, (xii) a time-of-flight mass analyzer, (xiii) an orthogonal acceleration time-of-flight mass analyzer, and (xiv) a linear acceleration time-of-flight mass analyzer And / or (h) one or more energy analyzers or electrostatic energy analyzers, and / or (i) one or more ion detectors, and / or (j) (i) a quadrupole mass. Filter, (ii) 2D or linear quadrupole ion trap, (iii) pole or 3D quadrupole ion trap, (iv) Penning ion trap One or more mass filters selected from the group consisting of: (v) an ion trap, (vi) a magnetic compartment mass filter, (vii) a time-of-flight mass filter, and (viii) a Wien filter, and / or (k) ions And / or (1) a device for converting a substantially continuous ion beam into a pulsed ion beam.

These mass spectrometers further
(I) a C trap and orbit trap (RTM) mass analyzer with an outer barrel electrode and a coaxial inner shaft electrode, in a first mode of operation, ions are transmitted to the C trap, and then the orbit Injected into a trap (RTM) mass analyzer and in a second mode of operation, ions are transferred to a C trap and then transferred to a collision cell or electron transfer dissociator, at least some ions split into split ions And then split ions are transmitted to the C trap before being injected into an orbital trap (RTM) mass analyzer, and / or (ii) ions are transmitted therein during use A stacked ring ion guide with a plurality of electrodes each having an opening, the electrode spacing increasing along the length of the ion path and in the upstream portion of the ion guide. The aperture in the electrode has a first diameter, the aperture in the electrode in the downstream portion of the ion guide has a second diameter smaller than the first diameter, and the opposite phase of the AC or RF voltage is used Any of the ion guides applied to the continuous electrode may be provided.

  These mass spectrometers may further comprise a device arranged and adapted to supply an AC or RF voltage to the electrodes. The AC or RF voltage is preferably (i) <50V vertex, (ii) 50-100V vertex, (iii) 100-150V vertex, (iv) 150-200V vertex, (v) 200-250V vertex (Vi) between 250-300V vertices, (vii) between 300-350V vertices, (viii) between 350-400V vertices, (ix) between 400-450V vertices, (x) between 450-500V vertices, and (xi )> Amplitude selected from the group consisting of> 500V vertices.

  The AC or RF voltage is preferably (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1 0.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1.5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0 to 3.5 MHz, (xii) 3.5 to 4.0 MHz, (xiii) 4.0 to 4.5 MHz, (xiv) 4.5 to 5.0 MHz, (xv) 5.0 to 5. 5 MHz, (xvi) 5.5-6.0 Hz, (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7 .5 to 8.0 MHz, (xxi) 8.0 .5MHz, (xxii) 8.5-9.0MHz, (xxiii) 9.0-9.5MHz, (xxiv) 9.5-10.0MHz, and (xxv)> 10.0MHz Frequency.

  Various embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings.

1 shows an ion mobility spectrometer according to a first embodiment of the present invention. 3 shows an ion mobility spectrometer according to a second embodiment of the present invention. 4 shows an ion mobility spectrometer according to a third embodiment of the present invention. 1 shows a switching device for switching an ion beam between an ion detector and an ion analyzer. 1 shows a switching device for switching an ion beam between an ion detector and an ion analyzer. 2 shows a flow diagram illustrating a portion of a method according to a preferred embodiment of the invention.

  FIG. 1 shows a block diagram of an ion mobility spectrometer according to a preferred embodiment. The apparatus comprises an entrance gate electrode 2, an ion capture region 3, an ion mobility separation (IMS) drift tube 5, and a detector 7. During operation, the ion beam 1 is received by the device. This beam may be a continuous ion beam or a discrete ion beam. The beam 1 may be received directly from the ion source and may pass through an analyzer or split / reaction region upstream of the capture region 3.

  Preferably, the capture region 3 is an RF confined ion guide. The capture region may be a rod set, a stacked ring design, or a coaxial structure. The capture region 3 is preferably maintained at a pressure of 0.1 to 10 torr by injection of buffer gas.

  According to operating modes well known in the art, ions are initially allowed to fill the capture region 3 during the accumulation period. During this period, the potential applied to the entrance gate electrode 2 is such that the ions 1 can enter the ion trapping region 3 while the exit gate electrode 4 has ions entering the trapping region 3. The potential is set so that it cannot be output. After the accumulation time T1, the potential applied to the entrance gate electrode 2 is changed so that ions cannot substantially enter the capture region 3. At the same time or after a delay time, the potential applied to the exit gate electrode 4 is changed so that ions can freely leave the capture region 3. The ions are then driven from the capture region 3 into the IMS separation drift tube 5. The ions are driven into the IMS device 5 by a DC field that acts on the ions to move in the direction from the entrance to the exit of the capture region 3, by a DC moving wave, by a pseudopotential drive force, or by a flow of buffer gas. obtain.

  Ions enter the IMS drift tube 5 with a relatively low temporal and spatial extent. After all ions have left the capture region 3, the potential applied to the exit gate electrode 4 is changed so that no further ions can exit the capture region 3, and the potential applied to the entrance gate electrode 2 is The next ion population is changed to start accumulating in the capture region 3. At the same time or after a short delay time, the ions are pushed down the ion mobility drift tube 5 by applying a DC field or a traveling wave. The drift tube 5 is preferably an RF confined ion guide composed of rod sets or stacked rings and operated at high pressure. While the first ion population is separated according to their drift time in the IMS device 5, the second ion population is accumulated in the capture region 3. When all ions exit the IMS drift tube 5 or when a predetermined IMS separation time is complete, the second ion set is ejected from the capture region 3 into the IMS separator 5 and the third ion set is Accumulated in the ion trap 3.

  Ions 6 leaving the IMS separator 5 are recorded on the detector 7. The ions pass through another analysis or fission / reaction region before being recorded by the detector 7.

  According to the conventional technique, the duration of the trapping period in the ion trap 3 is constant and is synchronized with the cycle time of the IMS separation using the drift tube 5. The ion trap 3 is used to increase the duty cycle of the device by trapping ions during the IMS separation cycle. However, such a technique may increase the charge density of the ions in the ion trap 3, and when ions are subsequently ejected from the ion trap 3 into the IMS drift tube 5, the charge density is reduced by the drift of the ions. It has been recognized that changing the time may increase the IMS peak width.

  According to a preferred embodiment of the present invention, the first time being passed through the IMS separator 5 and detected using the detector 7 in order to control the accumulation time of the subsequent ion population in the ion trapping region 3. The charge density of one ion population is used on or in combination with its own pre-recorded data. This accumulation time can be controlled so that the analytical performance control of the IMS device 5 is not impaired so that the total charge density entering the IMS device 5 from the ion trapping region 3 does not exceed a predetermined maximum value.

好ましくはＴ（ＩＭＳ）に等しい場合に許容される最大蓄積時間Ｔ（最大）。 For example, during operation, the first ion population P (1) is accumulated in the capture region 3 over time T1. This first population of ions is pulsed into the IMS drift tube 5 and the second population of ions P (2) is in the ion trap 3 over time T2 while IMS separation occurs over a time period T (IMS). And T2 = T (IMS). The charge density I (1) of the first ion population is measured by the detector 7, and the estimated charge density I (3) accumulated in the ion trap 3 with respect to the third ion population P (3) is predetermined. Is used to calculate the accumulation time T3 required to ensure that it is within the limit I (L). Where

Maximum accumulation time T (maximum) allowed, preferably when equal to T (IMS).

  After the first ion population is analyzed by the IMS device 5 and the detector 7, the second ion population is injected into the IMS device 5, and the third ion population P (3) remains in the ion trap 3 over time T 3. Accumulated in. Time period T3 may be less than T1 to reduce the charge density of the third ion population relative to the first ion population.

式中、Ｔｎは、イオントラップ３内の第ｎのイオン集団に対する蓄積時間を表す。Ｔ（ｎ−２）は、イオントラップ３内の第（ｎ−２）のイオン密度に対する蓄積時間を表す。Ｉ（Ｌ）は、ＩＭＳ飛行管５に入ることが所望される所定の電荷密度限界を表す。Ｉ（ｎ−２）は、第（ｎ−２）のイオン集団の電荷密度を表す。 After ions have accumulated in the ion trap 3 for time T3, these ions are kept in the ion trap for another time period time T (IMS) -T3 before being released into the IMS drift tube 5. . This ensures that the third ion population does not enter the drift tube 5 while the second ion population is separated into the drift tube 5. In general,

In the equation, Tn represents the accumulation time for the nth ion population in the ion trap 3. T (n−2) represents the accumulation time with respect to the (n−2) th ion density in the ion trap 3. I (L) represents the predetermined charge density limit that is desired to enter the IMS flight tube 5. I (n-2) represents the charge density of the (n-2) th ion population.

  This feedback control of the acquisition time of the capture region 3 can continue over many IMS cycles during the duration of the experiment time. The accumulation time of the ion trap 3 can vary between a maximum time T (maximum) approximately equal to the IMS drift time and a minimum accumulation time T (minimum). When T (n)> T (maximum), T (n) is set to T (maximum). When T (n) <T (minimum), T (n) = T (minimum).

  The present invention also contemplates other methods for controlling the ion population entering the IMS separator. For example, a single record of ion population prediction criteria can be used to study data trends to predict the charge density of subsequent ion populations, and thus adjust the accumulation time of this subsequent population based on this prediction. Instead of putting in data from a data set, several pre-recorded data sets may be used.

  In the exemplary method described, data from a single IMS separation experiment is used to adjust the population for subsequent single IMS separations. However, this data can be used to average or sum the data from a set of IMS experiments, each of which is acquired using approximately the same accumulation time, and then to predict the accumulation time for subsequent sets of IMS data. May be preferred.

  IMS separation can be combined or nested with chromatogram separations such as liquid or gas chromatography (LC or GC) to produce multi-dimensional data sets with high peak volumes.

  In the case of LC chromatography, the peak can be 1-10 seconds wide on the basis. In order to extract or record chromatographic peaks efficiently, it is desirable to record at least 10 extraction points during the elution time. Therefore, for a 1 second chromatographic peak, data should be recorded at 100 ms intervals. IMS separation time can be as large as 10 ms and individual mobility peaks can be less than 1 ms wide. Thus, a single 100 ms extraction can be recorded as the sum or average of 10 IMS separations. Each of these 10 IMS separations may be performed with approximately the same ion accumulation time, which is then determined based on the total charge density recorded during the initial 10 IMS cycles. It may vary for 10 IMS cycles.

  FIG. 5 shows a flowchart representing the above generalized feedback routine.

  Another embodiment of the present invention is to collect data from a short survey to determine the charge density of the input ion beam prior to each IMS separation or group of IMS separations. This survey data can be used to adjust the accumulation time for subsequent IMS separation cycles. For example, a survey experiment can be constructed by filling the capture region 3 over a predetermined short accumulation time. This population of ions can then be injected into the IMS device, moving the length of the drift tube 5 and directed to become incident on the detector 7. This data can then be used to predict the accumulation time for subsequent accumulations. In this embodiment, subsequent ion populations can be accumulated during the time that ions from the survey data are moving through the floating region. This can reduce the duty cycle and lower the total efficiency of extracting ions generated in the ion source.

  In order to increase the duty cycle in this embodiment, the passage time of ions through the drift tube 5 can be reduced by increasing the driving force through this region 5 during the investigation experiment. When using a DC driving force, the DC field can be increased to reduce the travel time of ions through the drift tube. Alternatively, if a moving DC field is used to drive the ions through the drift tube 5, the amplitude of the moving wave is increased so that the ions move with a moving wavefront that is independent of ion mobility. Or the velocity of the moving wave may be reduced. Thus, by changing the driving force during the survey scan, the resolution of the IMS during the survey scan deteriorates. However, since this data is only used to calculate the charge density, the ions need not be well separated during the survey scan. In this way, the time that a survey scan can be completed may be reduced to a small amount of time spent on analytical IMS separation, so that the experimental duty cycle is limited to a minimum amount when performing a survey scan. Reduced.

  Alternative methods are contemplated in which a survey scan can be performed without trapping ions in the upstream capture region. In this method, a continuous ion beam from the ion source is accelerated through the IMS suspension region 5 and the ion charge density is recorded by the detector 7. The charge density recorded during this research experiment can be used to calculate or set a desired accumulation time for a subsequent IMS experiment or group of IMS experiments.

  FIG. 2 shows another embodiment of the present invention that is similar to FIG. 1, wherein the same reference numbers denote corresponding devices. In the embodiment shown in FIG. 2, the electrode assembly 9 is arranged upstream of the ion trap 3 and the second ion detector 8 is arranged upstream of the IMS device 5.

  During operation, a survey data set for determining the charge density in the input ion beam 1 is recorded by directing some of the ions to the ion detector 8. The ion beam 1 may be a continuous ion beam, and an electrode assembly 9 may be used to switch ions while being received by the ion trap 3 and detector 8. If ions are received at the detector, their charge density per unit time can be measured. This value is then used to determine the accumulation time for the ions that should be accumulated in the ion trap 3 so as to prevent the charge density of ions implanted in the IMS device 5 from becoming too high. Can be used. An investigation of the input field density using the detector 8 can be performed during a portion of the period in which ions are separated in the IMS device 5 and detected on the detector 7. In this way, the duty cycle of the entire experiment can be maximized.

  A pulse lens assembly as described in US Pat. No. 7,683,314 may be used for the electrode assembly 8. In this disclosure, the ion beam is switched between full transmission and zero transmission with a variable duty cycle. It is contemplated that ions are directed towards the detector 8 during the low or zero duty cycle portion of the transmission cycle. Next, the signal detected on the detector 8 is used to dynamically adjust the duty cycle of the attenuating lens and / or the number of cycles of the pulse attenuating lens during the fixed accumulation time of the ion trapping region 3. Can do. Other types of attenuation devices may be used.

  The electrode assembly 9 can be used to direct a small proportion of known input ions towards the detector 8 while directing the rest of the ions towards the capture region 3. The accumulation time in the capture area 3 can then be changed based on the signal detected by the detector 8. Alternatively, the survey data may be acquired by accumulating ions in the capture region 3 over a short period of time rather than passing the ions through the IMS separation region 5. This may be an advantageous mode of operation when the ion transit time from the capture region 3 to the detector 8 is less than the transit time from the capture region 3 to the detector 7. This allows a survey scan to be performed over a time period shorter than the IMS separation time, thus increasing the total duty cycle of acquisition.

  The detector 8 can be a collapsible detector such as an electron multiplier or Faraday plate, or a non-collapsible detector such as a series inductive charge detector.

  The IMS device 5 can be combined with another upstream analyzer such as a quadrupole mass filter or a differential ion mobility filter. Additionally or alternatively, the IMS device 5 can be combined with one or more downstream analyzers such as a quadrupole mass filter or a time-of-flight mass filter. However, when used with a second downstream device that limits the total charge transmitted, such as a resolving quadrupole mass filter, the signal reaching the ion detector 7 cannot represent the charge density entering the IMS device 5 It is important to keep in mind. To overcome this problem, the second downstream device can be switched to a mode to allow full transmission of the ion population representing the ion population prior to the second downstream device, or the charge of the ions A separate ion detector can be placed upstream of the second downstream device to measure density.

  FIG. 3 shows an embodiment in which the mass analyzer is arranged downstream of the drift tube 5. The embodiment of FIG. 3 is similar to FIG. 2 and the same elements are labeled with the same reference numbers. In the embodiment of FIG. 3, a resolving quadrupole mass filter 12 is placed after the IMS drift tube 5. When the mass filter 12 sorts ions, the ion current recorded by the detector 7 does not represent the charge density of the input ion beam 1. The apparatus can be operated in an investigation mode where the quadrupole rod set 12 is set to an RF only mode such that all mass to charge ratios are transmitted. The signal measured by the detector 7 can then be used to control the accumulation time of the ion trapping region 3.

  As an alternative to operating the mass filter 12 in unsorted mode, an additional detector 10 is placed downstream of the IMS drift tube 5 so that ions can be passed through the detector 10 without being transmitted through the mass filter. May be. A switched or convertible electrode arrangement 11 may be used to guide ions exiting the IMS drift tube 5 to the detector 10 during the survey scan. The signal recorded on the detector 10 can then be used to adjust the accumulation time of ions in the capture region 3.

  4A and 4B show an embodiment of a device that can be used to switch ions between an ion detector and an analyzer. Such an apparatus can be used to switch ions to the detector 8 in the embodiment of FIG. 2 and to switch ions to the detector 10 in the embodiment of FIG. 4A and 4B show Rev. Sci. Instrum. , Vol. 48, no. 8 shows a notation of a quadrupole electrostatic lens such as that described in August 1977. This device comprises four electrodes having a parabolic internal electrode surface. FIG. 4A shows the device in a mode in which the input ion beam 15 is directed towards the ion detector 13. FIG. 4B shows the device in an operating mode in which the input beam 15 is directed towards the downstream analyzer 14. Other methods of splitting or redirecting the ion beam are also contemplated.

  In the above embodiment, the total charge entering the upstream capture region 3 is controlled within a predetermined value. However, in some cases, the performance of the IMS device can be adversely affected for charge densities within a specific range of ion mobility without being significantly adversely affected by the total charge density entering the flight tube. Ions having a mobility outside that range are not significantly adversely affected even if the total number of ions in the IMS device is large. This effect arises due to the time difference in which ions from different species are close together in the IMS drift tube. For example, if the ion population ejected into the drift tube is composed of ions from many different analytes, all of these ions remain only at ion implantation points within a narrow band within the drift tube. These ions separate from each other into different zones or regions of the drift tube as they are pushed along the drift tube. However, some of the population of ions with the same ion mobility remains in a narrow band and therefore remains very close to most or all of the drift tube length. The effects of space charge interactions on these ions can be significant, especially when the charge density is high within this mobility range. Some of the populations of ions with low charge density and different mobility that are separated from high charge density species may be affected by space charge interactions over a short period of time, and thus for these species, The peak shape distortion and / or drift time shift is not very large.

  In this case, it is desirable not to control the total charge injected into the drift tube, but to control the charge density within a specific drift time range. Although the charge must be measured after IMS separation has occurred, any of the described methods for controlling the total charge density injected into the drift tube 5 can be used. Several embodiments of this method are contemplated.

  For example, a detector 7 or 10 may be used to record the IMS drift time chromatogram, and the ion accumulation time in the ion capture region 3 or of ions preceding that capture region 3 during a fixed accumulation time. To control the decay, the total charge density within a particular region or regions of this chromatogram may be measured and used. Alternatively, the IMS device 5 allows the gate electrode to only allow the selected drift time region (s) or multiple drift time regions (s) to reach the detector 7 or 10 during the IMS cycle. May be placed after. In this case, data recorded from a plurality of drift time regions may be added to a single charge density value or individually queried. In both of these cases, it is an intention to keep the charge density of an ion population with a particular mobility or drift time through the IMS device at a predetermined maximum value by changing the conditions during the accumulation period. This may also be combined with controlling the maximum total charge injected into the capture region. However, this maximum total charge is greater than the charge allowed for a particular drift time region.

  Note that IMS device 5 is used with a downstream mass analyzer and the charge density recorded within a specific range of mass to charge ratio is used to estimate or estimate the charge density within a specific drift time range. Should. This is due to the strong positive correlation between the mass to charge ratio and the IMS drift time.

  When the IMS device is coupled with a downstream analyzer, such as a time-of-flight analyzer, the peak shape and / or drift time measurements within a particular drift time range or range (s) are determined by the space within the IMS device. It is preferred to use charge density within a specific range (s) or range (s) to control the total ion population entering the IMS device so that it is not compromised due to charge interactions.

  In all cases discussed, it is preferable to record a value that represents the decay of the ion population being applied. This value can be used to readjust the intensity of the data recorded during acquisition and represent the intensity of the input ion beam before attenuation. This maintains the quantitative performance of the system even if some ions are disposed of.

  Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that various changes in form and detail may be made without departing from the scope of the invention as set forth in the appended claims. Will be understood.

  For example, although the ions are described as being stored in the upstream trap 3 only once per IMS cycle, the present invention provides for ions to be delivered to the trap 3 or fixed or variable It should be noted that a mode that allows entry into the capture region 3 as a series of ion packets during the accumulation time is also considered.

  In cases where there is a fixed accumulation time, the continuous input ion beam can be switched or dammed between high and low transmission during the accumulation time. The duty cycle of the gate voltage can be varied to produce the desired charge density stored in the capture region and to allow control of the ion population ejected into the IMS device 5. Such a gating device and method for accumulating ion populations in a trap is described in US Publication No. 2012/0119078. Advantageously, the number of distinct gate periods during the accumulation time is reproducible. Thus, the number of accumulation periods and the total accumulation period, and hence the IMS cycle time, are preferably synchronized so that a reproducible integer number of ion beam gate periods occurs every total accumulation time period.

  Although it is preferred that the gate period (s) or period (s) be synchronized to the IMS isolation cycle time, it is also contemplated that the accumulation period (s) or period (s) cannot be synchronized to the IMS isolation cycle time. In this case, there may be uncertainty in the charge density accumulated in the capture region 3 prior to injection into the IMS device 5. If this uncertainty, or the time error in which ions are allowed to fill the capture region 3, is small compared to the total accumulation time, the described method is sufficient and departs from the spirit of the invention. And will still control the ion population.

  In another method, ions may be accumulated for a fixed period of time, and a defocus lens is used to attenuate the input ion beam so that it does not exceed the target charge density injected into the IMS separator. Such an upstream damping device may be used.

  In another method, ions may be accumulated in the upstream ion trapping region for a fixed time, but only a portion of the total charge density in the trapping region is released into the IMS device. The amount of charge released from the capture region can be controlled to be within a predetermined maximum value by using, for example, the above method. This can be accomplished by providing a gate electrode at the exit of the capture region and pulsing the gate electrode potential one or more times so that ions are allowed to exit the capture region for a variable time period. Alternatively, the ion population in the capture region can be divided into several populations of known charge density, and then only a certain number of these subpopulations are released into the IMS device. Ion populations can be segmented within a segmented RF confined ion guide by applying a DC potential to several segments to form a plurality of axial DC potential wells.

  Using the present invention, the ion population is controlled and Belov et al., Anal Chem. 2007 March 15; 79 (6): 2451-1462. MULTIPLEXED ION MOBILITY SPECTROMETRY-ORTHOGONAL TIME-OF-FLIGHT MASS SPECTROMETRY-implanted ions, such as those described in, can be reduced due to the effect of space charge interaction. Rather than changing the number of ion packets injected per IMS cycle to control the charge density of each packet, a fixed number of ion packets can be released into the IMS device per cycle.

  The disclosed invention may be combined with an upstream high capacity ion trap from which ions are mass selectively ejected. Examples of such devices are described in International Application No. PCT / GT2008 / 002981 or US Application No. 12/676154. In this application, a high volume, low performance analytical ion trap is placed within a high performance, low volume analytical ion trap. An attenuation device is placed in the two traps. In operation, ions are mass selectively ejected from the upstream low performance ion trap into the high performance ion trap, and ions are ejected and detected from the high performance ion trap almost simultaneously, thus creating a mass spectrum. Thus, only the upstream analytical ion trap will contain a portion of the total ion population at any time during its analytical scan. This reduces the likelihood that the analytical performance of this second ion trap will be compromised due to space charge interactions. In addition, after a survey mass spectrum has been obtained by mass selective ejection from one or both of the ion traps, the ion population in the downstream analytical ion trap may be subjected during any part of this associated scanning process. The transmission of a portion of the total ion population with different mass-to-charge ratios exiting the upstream ion trap can be dynamically adjusted so as not to exceed a predetermined upper limit.

  This low performance analytical ion trap and attenuator can be located upstream of the capture region 3. Based on a mass-to-charge ratio survey scan of the ion population upstream of the trap and a known correlation between mass-to-charge ratio and IMS drift time, when ions are accumulating in the capture region of the IMS device In addition, the attenuating lens can change dynamically so that charge densities within a specific mass-to-charge ratio range (and hence a specific estimated mobility range) can be controlled within the required limits. The ions can accumulate in the capture region 3 at about the same time that the ions are ejected from the upstream low performance high capacity ion trap. Ion transmission between the upstream high volume analytical ion trap and the IMS capture region 3 is controlled by an attenuating lens during this process. After the ions are accumulated in the IMS capture region 3, the population is released into the IMS device 5 and can be separated as described above.

  It is preferred to record a value representing the decay of the ion population applied over each mass to charge ratio range while filling the IMS capture region 3. This value can be used to readjust the intensity of the data recorded during acquisition and represent the intensity of the input ion beam before attenuation. Thereby, even if some ions are disposed of, the quantitative performance of the system can be maintained.

Claims (17)

A method for analyzing ions by ion mobility separation or mass separation,
Providing an ion mobility separator isolation region (IMS) and an ion trap for emitting ion packets into the IMS;
For each ion packet released from the ion trap into the IMS, selecting a predetermined maximum charge desired to be released into the IMS;
Discharging a first ion packet from the ion trap;
Detecting the charge of ions in the first ion packet using a detector;
Determining a difference between the charge detected by the detector and the predetermined maximum charge;
Discharging a second subsequent ion packet from the ion trap into the IMS, wherein the formation of the second ion packet is such that the charge of the ions in the second ion packet is the predetermined maximum charge. An emission that is controlled based on the difference between the charge detected in the first ion packet and the predetermined maximum charge to be substantially the same as or less than To do
Said method.   Ions are allowed to enter the ion trap during an ion accumulation period and will be trapped in the ion trap, and the first ion packet accumulates in the ion trap over a first accumulation period. And the second ion packet is accumulated in the ion trap over a second accumulation period, and the duration of the second accumulation period is the charge of the ions detected in the first ion packet. The method of claim 1, wherein the method is selected or modified for the first accumulation period based on a difference between the first accumulation period and the predetermined maximum charge.   Ions are induced at an ion filling rate within the ion trap, trapped within the ion trap during an ion accumulation period, and the first ion packet accumulates at a first ion filling rate within the ion trap. And the second ion packet is accumulated in the ion trap at a second ion filling rate, the second filling rate being determined by the charge of the ions detected in the first ion packet and the 3. The method of claim 1 or 2, wherein the method is selected or changed for the first fill rate based on the difference between a predetermined maximum charge.   Only a portion of the ions in the ion trap are ejected during the discharge of each ion packet from the ion trap, and the size of the portion ejected into the second ion packet is the first Based on the difference between the charge of the ions detected in the ion packet and the predetermined maximum charge, it is selected or changed for the size of the portion ejected in the first ion packet The method of claim 1.   The first ion packet enters the detector through the IMS and is driven by an electric field such that ions pass through the IMS, and the electric field causes ions in the first ion packet to pass through the IMS. 5, and varies with time so that corresponding ions in the second ion packet are driven at low speeds through the IMS. Method.   A mass analyzer is provided downstream of the IMS and upstream of the detector for mass analysis of ions that have passed through the IMS, the mass analyzer being configured such that the first ion packet is substantially transmitted by the mass analyzer. The first ion packet bypasses the mass analyzer and then passes through the detector, the mass analyzer being in the second mode. 6. The ion packet is operated in a second mode such that the ion packet is attenuated by the mass analyzer during mass analysis therein, or the second ion packet does not bypass the mass analyzer. The method according to any of the above.   A mass analyzer and the detector are provided downstream of the IMS, the first ion packet is directed to the detector without passing through the mass analyzer, and the second ion packet is directed to the mass analyzer. 6. The method of any one of claims 1-5, wherein the method is induced.   5. The method of any one of claims 1-4, wherein the detector is provided upstream of the IMS and the first ion packet is emitted from the ion trap to the detector.   Detecting the charge of the ions in the second ion packet using a detector and determining the difference between the charge of the ions detected in the second ion packet and the predetermined maximum charge And discharging a third subsequent ion packet from the ion trap to the IMS, wherein the formation of the third ion packet comprises the charge of ions in the third ion packet being Based on the difference between the charge detected in the second ion packet and the predetermined maximum charge such that it is substantially equal to or less than the predetermined maximum charge. 9. The method according to any one of claims 1 to 8, which is controlled. The predetermined maximum charge is the maximum charge amount of ions within a predetermined drift time range through the IMS that is desired to be pulsed into the IMS in an ion packet;
The first ion packet is detected by the detector after the ions have passed through the IMS, and the detector has an ion in the first ion packet having a drift time within the predetermined drift time range. And the detected charge is compared to a predetermined maximum charge, and using the comparison, ions in the second ion packet having a drift time within the predetermined drift time range are 10. The formation of the second ion packet according to any of claims 1 to 9, wherein the formation of the second ion packet is controlled to have a total charge that is substantially the same as or less than a predetermined maximum charge. Method. The predetermined maximum charge is the maximum charge amount of ions within a predetermined drift time range through the IMS that is desired to be pulsed into the IMS in an ion packet;
It is assumed that ions having the predetermined drift time range have a predetermined mass-to-charge ratio range, and the first ion packet is mass analyzed and within this packet having the predetermined mass-to-charge ratio range The total charge of the ions is detected,
The detected charge is compared with the predetermined maximum charge, and using the comparison, ions in the second ion packet having a drift time within the predetermined drift time range are substantially equal to the predetermined maximum charge. 10. The method of any one of claims 1-9, wherein the formation of the second ion packet is controlled to have a total charge that is substantially the same or less. A method for analyzing ions by ion mobility separation or mass separation,
Providing an ion mobility separator separation region (IMS) and an ion trap for discharging ion packets into the IMS;
In each ion packet emitted from the ion trap, selecting a predetermined maximum charge desired to be released into the IMS;
Directing ions from an ion source to a detector and detecting the rate at which charge is received at the detector due to ions from the ion source being detected;
Directing ions from the ion source into the ion trap and capturing the ions only during an ion accumulation period;
Selecting the duration of the ion accumulation period, or such that the charge of the ions trapped in the ion trap is substantially equal to or less than the predetermined maximum charge. Controlling the attenuation of ions moving towards the ion trap during the accumulation period;
Discharging the ions from the ion trap into the IMS;
Said method.   The method of claim 12, wherein the detector is provided upstream of the IMS.   14. Any one of claims 1-9, 12 or 13, wherein the predetermined maximum charge is the total charge desired to be pulsed into all of the ions in an ion packet and into the IMS. The method according to claim 1.   A first electric field condition is applied in the IMS such that ions passing through the IMS separate according to their ion mobility, operating a first mode of operation, and / or ions passing through the IMS 15. The method of any of claims 1-14, comprising operating a second mode of operation, wherein a second electric field condition is applied in the IMS to separate according to their mass to charge ratio. An ion mobility separator separation region (IMS), an ion trap for discharging ion packets into the IMS, and a detector;
Discharging a first ion packet from the ion trap;
Using the detector to detect the charge of ions in the first ion packet;
Determining a difference between the charge detected by the detector and a predetermined maximum charge desired to be released into the IMS in each ion packet emitted from the ion trap into the IMS; And the formation of the second ion packet is such that the charge of ions in the second ion packet is substantially equal to or less than the predetermined maximum charge. Arranged and adapted to emit a second subsequent ion packet from the ion trap into the IMS, controlled based on the difference between the charge detected in and the predetermined maximum charge. Control means,
An ion mobility spectrometer or a mass spectrometer. An ion source, an ion mobility separator separation region (IMS), an ion trap for emitting ion packets into the IMS, and a detector;
Directing ions from the ion source to the detector and detecting the rate at which charge is received at the detector due to ions detected from the ion source;
Directing ions from the ion source into the ion trap, capturing the ions only during the ion accumulation period;
It is desirable that the duration of the ion accumulation period is selected or that the charge of the ions trapped in the ion trap is released into the IMS in each ion packet emitted from the ion trap. Controlling the attenuation of ions moving toward the ion trap during the accumulation period so that they are substantially equal to or less than the maximum charge to be removed, and removing the ions from the ion trap to the IMS An ion mobility spectrometer or mass spectrometer comprising control means arranged and adapted to release into.

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